Insights from the Menstrual Cycle in Pulmonary Arterial Hypertension.
Ann Am Thorac Soc
; 18(2): 218-228, 2021 02.
Article
en En
| MEDLINE
| ID: mdl-32885987
Rationale: Sex hormones play a role in pulmonary arterial hypertension (PAH), but the menstrual cycle has never been studied.Objectives: We conducted a prospective observational study of eight women with stable PAH and 20 healthy controls over one cycle.Methods: Participants completed four study visits 1 week apart starting on the first day of menstruation. Relationships between sex hormones, hormone metabolites, and extracellular vesicle microRNA (miRNA) expression and clinical markers were compared with generalized linear mixed modeling.Results: Women with PAH had higher but less variable estradiol (E2) levels (P < 0.001) that tracked with 6-minute walk distance (P < 0.001), N-terminal prohormone of brain natriuretic peptide (P = 0.03) levels, and tricuspid annular plane systolic excursion (P < 0.01); the direction of these associations depended on menstrual phase. Dehydroepiandrosterone sulfate (DHEA-S) levels were lower in women with PAH (all visits, P < 0.001). In PAH, each 100-µg/dl increase in DHEA-S was associated with a 127-m increase in 6-minute walk distance (P < 0.001) and was moderated by the cardioprotective E2 metabolite 2-methoxyestrone (P < 0.001). As DHEA-S increased, N-terminal prohormone of brain natriuretic peptide levels decreased (P = 0.001). Expression of extracellular vesicle miRNAs-21, -29c, and -376a was higher in PAH, moderated by E2 and DHEA-S levels, and tracked with hormone-associated changes in clinical measures.Conclusions: Women with PAH have fluctuations in cardiopulmonary function during menstruation driven by E2 and DHEA-S. These hormones in turn influence transcription of extracellular vesicle miRNAs implicated in the pathobiology of pulmonary vascular disease and cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
MicroARNs
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Hipertensión Arterial Pulmonar
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Hipertensión Pulmonar
Tipo de estudio:
Observational_studies
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Prognostic_studies
Límite:
Female
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Humans
Idioma:
En
Revista:
Ann Am Thorac Soc
Año:
2021
Tipo del documento:
Article
Pais de publicación:
Estados Unidos